Limits...
Mapping genetically controlled neural circuits of social behavior and visuo-motor integration by a preliminary examination of atypical deletions with Williams syndrome.

Hoeft F, Dai L, Haas BW, Sheau K, Mimura M, Mills D, Galaburda A, Bellugi U, Korenberg JR, Reiss AL - PLoS ONE (2014)

Bottom Line: Univariate and multivariate pattern classification results of morphometric brain patterns complemented by behavior implicate a possible role for the chromosomal region that includes: 1) GTF2I/GTF2IRD1 in visuo-spatial/motor integration, intraparietal as well as overall gray matter structures, 2) the region spanning ABHD11 through RFC2 including LIMK1, in social cognition, in particular approachability, as well as orbitofrontal, amygdala and fusiform anatomy, and 3) the regions including STX1A, and/or CYLN2 in overall white matter structure.This knowledge contributes to our understanding of the role of genetics on human brain structure, cognition and pathophysiology of altered cognition in WS.The current study builds on ongoing research designed to characterize the impact of multiple genes, gene-gene interactions and changes in gene expression on the human brain.

View Article: PubMed Central - PubMed

Affiliation: Center for Interdisciplinary Brain Sciences Research (CIBSR), Stanford University School of Medicine, Stanford, CA, United States of America; Department of Neuropsychiatry, Keio University, School of Medicine, Tokyo, Japan.

ABSTRACT
In this study of eight rare atypical deletion cases with Williams-Beuren syndrome (WS; also known as 7q11.23 deletion syndrome) consisting of three different patterns of deletions, compared to typical WS and typically developing (TD) individuals, we show preliminary evidence of dissociable genetic contributions to brain structure and human cognition. Univariate and multivariate pattern classification results of morphometric brain patterns complemented by behavior implicate a possible role for the chromosomal region that includes: 1) GTF2I/GTF2IRD1 in visuo-spatial/motor integration, intraparietal as well as overall gray matter structures, 2) the region spanning ABHD11 through RFC2 including LIMK1, in social cognition, in particular approachability, as well as orbitofrontal, amygdala and fusiform anatomy, and 3) the regions including STX1A, and/or CYLN2 in overall white matter structure. This knowledge contributes to our understanding of the role of genetics on human brain structure, cognition and pathophysiology of altered cognition in WS. The current study builds on ongoing research designed to characterize the impact of multiple genes, gene-gene interactions and changes in gene expression on the human brain.

Show MeSH

Related in: MedlinePlus

Schematic diagram of deleted genes in WS and in partial deletion participants (AWSdel).Genes listed in the figure are either ones known to be expressed in the brain and are important for neurodevelopment, synaptic plasticity and neuronal reorganization: LIMK1[54], FZD9[55], STX1A[56], CYLN2[57], GTF2 I[58] and GTF2IRD1[59], or are break-points.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4126723&req=5

pone-0104088-g001: Schematic diagram of deleted genes in WS and in partial deletion participants (AWSdel).Genes listed in the figure are either ones known to be expressed in the brain and are important for neurodevelopment, synaptic plasticity and neuronal reorganization: LIMK1[54], FZD9[55], STX1A[56], CYLN2[57], GTF2 I[58] and GTF2IRD1[59], or are break-points.

Mentions: To further gain a better understanding of the neurogenetic basis of human behavior using this ‘model disease’ approach, the current study undertook a targeted investigation of persons with WS having rare atypical deletions (AWSdel) by comparing these individuals to WS and TD groups. While most individuals with WS exhibit the full ‘classic deletion,’ there are rare cases (∼2%) where relatively smaller deletions occur [10]. It is currently unknown how smaller WS deletions impact brain structure in WS. By investigating AWSdel, new insights into the role of specific genes on brain and behavior can be obtained. To accomplish this goal, we collected brain imaging data and behavioral data from samples of AWSdel, WS and TD. There were three types of deletions among the AWSdel cases; i.e., one where the genes GTF2I and GTF2IRD1 were spared, another where the region from TRIM50/FKBP6 to (but not including) STX1A was spared, and a third where small deletions occurred between ABHD11 through RFC2 including LIMK1 (Figure 1). We focused on visuo-spatial and social cognition, two key phenotypes of WS and examined whether each AWSdel case resembled WS or TD. The overarching objective of this investigation was to deduce gene-brain-behavior associations by examining genes that are commonly deleted in those with similar neuroanatomical and behavioral profiles among individuals comprising our AWSdel sample (Figure 1).


Mapping genetically controlled neural circuits of social behavior and visuo-motor integration by a preliminary examination of atypical deletions with Williams syndrome.

Hoeft F, Dai L, Haas BW, Sheau K, Mimura M, Mills D, Galaburda A, Bellugi U, Korenberg JR, Reiss AL - PLoS ONE (2014)

Schematic diagram of deleted genes in WS and in partial deletion participants (AWSdel).Genes listed in the figure are either ones known to be expressed in the brain and are important for neurodevelopment, synaptic plasticity and neuronal reorganization: LIMK1[54], FZD9[55], STX1A[56], CYLN2[57], GTF2 I[58] and GTF2IRD1[59], or are break-points.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126723&req=5

pone-0104088-g001: Schematic diagram of deleted genes in WS and in partial deletion participants (AWSdel).Genes listed in the figure are either ones known to be expressed in the brain and are important for neurodevelopment, synaptic plasticity and neuronal reorganization: LIMK1[54], FZD9[55], STX1A[56], CYLN2[57], GTF2 I[58] and GTF2IRD1[59], or are break-points.
Mentions: To further gain a better understanding of the neurogenetic basis of human behavior using this ‘model disease’ approach, the current study undertook a targeted investigation of persons with WS having rare atypical deletions (AWSdel) by comparing these individuals to WS and TD groups. While most individuals with WS exhibit the full ‘classic deletion,’ there are rare cases (∼2%) where relatively smaller deletions occur [10]. It is currently unknown how smaller WS deletions impact brain structure in WS. By investigating AWSdel, new insights into the role of specific genes on brain and behavior can be obtained. To accomplish this goal, we collected brain imaging data and behavioral data from samples of AWSdel, WS and TD. There were three types of deletions among the AWSdel cases; i.e., one where the genes GTF2I and GTF2IRD1 were spared, another where the region from TRIM50/FKBP6 to (but not including) STX1A was spared, and a third where small deletions occurred between ABHD11 through RFC2 including LIMK1 (Figure 1). We focused on visuo-spatial and social cognition, two key phenotypes of WS and examined whether each AWSdel case resembled WS or TD. The overarching objective of this investigation was to deduce gene-brain-behavior associations by examining genes that are commonly deleted in those with similar neuroanatomical and behavioral profiles among individuals comprising our AWSdel sample (Figure 1).

Bottom Line: Univariate and multivariate pattern classification results of morphometric brain patterns complemented by behavior implicate a possible role for the chromosomal region that includes: 1) GTF2I/GTF2IRD1 in visuo-spatial/motor integration, intraparietal as well as overall gray matter structures, 2) the region spanning ABHD11 through RFC2 including LIMK1, in social cognition, in particular approachability, as well as orbitofrontal, amygdala and fusiform anatomy, and 3) the regions including STX1A, and/or CYLN2 in overall white matter structure.This knowledge contributes to our understanding of the role of genetics on human brain structure, cognition and pathophysiology of altered cognition in WS.The current study builds on ongoing research designed to characterize the impact of multiple genes, gene-gene interactions and changes in gene expression on the human brain.

View Article: PubMed Central - PubMed

Affiliation: Center for Interdisciplinary Brain Sciences Research (CIBSR), Stanford University School of Medicine, Stanford, CA, United States of America; Department of Neuropsychiatry, Keio University, School of Medicine, Tokyo, Japan.

ABSTRACT
In this study of eight rare atypical deletion cases with Williams-Beuren syndrome (WS; also known as 7q11.23 deletion syndrome) consisting of three different patterns of deletions, compared to typical WS and typically developing (TD) individuals, we show preliminary evidence of dissociable genetic contributions to brain structure and human cognition. Univariate and multivariate pattern classification results of morphometric brain patterns complemented by behavior implicate a possible role for the chromosomal region that includes: 1) GTF2I/GTF2IRD1 in visuo-spatial/motor integration, intraparietal as well as overall gray matter structures, 2) the region spanning ABHD11 through RFC2 including LIMK1, in social cognition, in particular approachability, as well as orbitofrontal, amygdala and fusiform anatomy, and 3) the regions including STX1A, and/or CYLN2 in overall white matter structure. This knowledge contributes to our understanding of the role of genetics on human brain structure, cognition and pathophysiology of altered cognition in WS. The current study builds on ongoing research designed to characterize the impact of multiple genes, gene-gene interactions and changes in gene expression on the human brain.

Show MeSH
Related in: MedlinePlus